Embolization is a minimally invasive procedure to selectively occlude blood vessels by intentionally introducing embolic agents into the blood vessels. Generally, the embolization procedure is carried out by percutaneous insertion of a catheter into the desired blood vessel (artery or vein) under X-ray fluoroscopy guidance. Once in place, an embolic agent is then deployed to stop blood flow by either direct occlusion of the blood vessel or induction of local thrombosis, or both.
Embolization is applied to treat various conditions whereby occlusion of blood vessels is beneficial. For example, such conditions may include but are not limited to traumatic hemorrhage, bleeding from gastrointestinal or respiratory tracts, arteriovenous malformations (AMVs), aneurysm, uterine fibroids, transcatheter arterial chemoembolization (TACE) and selective internal radiation therapy (SIRT) for unresectable liver tumors.
To date liver cancer is the third leading cause of cancer death worldwide and is highly prevalent in Asia. Less than 30% of primary liver cancer patients and less than 10% of metastatic liver cancer patients may be eligible for surgical removal while the remaining patients may only turn to palliative treatments such as TACE and SIRT.
Generally in TACE, the hepatic artery is embolized following delivery of chemotherapeutic agents into the artery. The purpose of the embolization of the hepatic artery is twofold being (i) to prevent the washout of the therapeutic drug at the site of tumor and (ii) to induce tumor ischemia. The desired outcome is to enhance the efficacy of chemotherapy while reducing systemic exposure. In TACE, repeat procedures are common so patency of the hepatic arteries needs to be restored before a subsequent TACE is performed. Therefore, temporary occlusion of the hepatic artery using a biodegradable agent is desirable. In this procedure, Gelfoam, a biodegradable gelatin sponge, is typically used. It may be cut into small pledgets (about 1 mm or larger) and delivered as a particulate embolic agent.
In other instances, occlusion of vessels may be required to divert blood flow or to protect the vascular territory from reflux of toxic materials: For example in SIRT of liver cancers, radio-active particles are delivered into the hepatic artery and the gastroduodenal artery (GDA) is often prophylactically embolized to prevent reflux of the radioactive particles into the stomach and small intestines as the radioactive particles cause radiation ulcers which often lead to devastating gastrointestinal hemorrhages. Currently, solid embolic device in the form of coil may be used Coil-form solid embolic devices are usually made of metals (e.g., stainless steel, platinum or nitinol alloys) and are therefore non-biodegradable. As the reflux prophylaxis is only relevant during delivery of the radioactive particles, permanent occlusion of the GDA is unnecessary and biodegradable embolic may be desirable in such a situation.
Currently, there are limited types of biodegradable embolic devices available. In this regard, Gelfoam may be considered the most widely used biodegradable embolic agent for intravascular embolization. It may be typically resorbed in days to weeks depending on the amount of uses, the degree of fluid saturation and the site of use. However, permanent occlusion may occur by residual organized thrombi or fibrotic change of the vessel. In addition, the occlusion level may be unpredictable because of the irregular shape and variability in size of the Gelfoam. In general, Gelfoam tends to aggregate in vessels more proximally than intended, and significantly small fragments of Gelfoam may migrate into capillary beds. Therefore, it is difficult to perform controlled target embolization using these agents. Occlusin™ 500 Artificial Embolization Device (OCL 500, IMBiotechnologies Ltd., Edmonton (Alberta), Canada) is another biodegradable embolic agent for highly vascularised tumors. The agent consists of biodegradable poly-lactic-co-glycolic acid (PLGA) microspheres coated with type I bovine collagen. Although OCL 500 is manufactured in multiple size ranges, there is a risk of migration of microspheres during the administration process. Yet another type of embolic agent is a biodegradable liquid embolic agent and fibrin glue may currently be the only one available in the market. However, despite its good biocompatibility, the use of fibrin glue is hindered by its fast degradation and need for double-lumen catheterization.
Accordingly, there is a need for a biodegradable embolic device (e.g., a biodegradable embolic foam or plug) that precisely occludes the blood vessel and degrades at a predictable rate, thereby addressing at least the problems above. This aims to facilitate recanalization of the blood vessels and allow embolization procedures to be repeated, especially in liver cancer treatment.